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5th June 2013 @ 04:24

Procedure:

Ethyl acetoacetate (8.2 mL, 62.8 mmol, 1 equiv.), K2CO3 (11.4 g, 82.4 mmol, 1.3 equiv.) and sodium iodide (10.3 g, 68.9 mmol, 1.1 equiv.) were dissolved in acetonitrile (120 mL) and cooled in ice water. A yellow colour was observed in the mixture. Chloroacetone (6.4 mL, 79.9 mmol, 1.3 equiv.) was added dropwise and the reaction mixture stirred for 5 minutes prior to heating to reflux. 

Followed by TLC - after four hours reaction had reached completion and was left to reach room temperature and concentrated under reduced pressure to leave an orange liquid. The liquid was dissolved in ethyl acetate (~90 mL) and washed with water (2 x 20 mL) and brine (20 mL). The organic layer containing the intermediate was concentrated under reduced pressure to a brown liquid and 4-fluoroaniline (8.2 mL, 63.8 mmol, ~0.6 equiv.) was added. This mixture was heated to 90 °C, after 3.5 hours reaction was complete. The black reaction mixture was cooled, dissolved in EtOAc (40mL) and washed with water (3 × 20 mL) and brine (20 mL), dried over MgSO4, filtered and evaporated to give a black liquid - still contains 4-fluoroaniline so purified by flash column chromatography over silica (5% EtOAc in Hexane) to give an orange semi-solid containing residual EtOAc - see 1H NMR, which was dried to give an orange semi-solid (12.5 g, 47.8, 76%).

Data:

TLC (10% EtOAc in Petrol)

AEW 7-3 10% EtOAc in Petrol.png

1H NMR (contains EtOAc)

AEW 7-3 - H.pdf

Hazard and Risk Assessment:

See Synthesis of Ethyl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate (AEW 7-1) and

Synthesis of Ethyl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate (AEW 7-2)

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Attached Files
AEW 7-1.png
AEW 7-3 10% EtOAc in Petrol.png
AEW 7-3 - H.pdf